TMEM-MRI: A Pilot Feasibility Study of MRI for Imaging of TMEM in Patients With Operable Breast Cancer

Официальное название

TMEM-MRI: A Pilot Feasibility Study of Magnetic Resonance Imaging for Imaging of TMEM (Tumor Microenvironment of Metastasis) in Patients With Operable Breast Cancer

Обзор

The aim of this study is to assess feasibility of a new imaging technology in the management of breast cancer - Tumor Microenvironment of Metastasis - Magnetic Resonance imaging (TMEM-MRI).

Подробное описание

The primary objective of this study is to develop a magnetic resonance imaging (MRI) based method for assessing TMEM-mediated permeability associated with cancer cell dissemination in breast cancer patients. TMEM-MRI has the ability to detect tumor areas with more leakiness (perfusion), where cancer cells enter blood vessels to travel to other sites. This novel TMEM-MRI has potential to be used in clinical practice to identify tumors with high leakiness that might have higher chances to recur after breast cancer treatment. In addition, TMEM-MRI can potentially be used to assess response to preoperative treatments (chemotherapy, hormonal therapy) over time.

In a prior study, it was found that patients with high TMEM doorway score, compared to patients with mid/low TMEM doorway score, in their residual disease after neoadjuvant therapy, had worse distant relapse-free survival (p = 0.008). These results demonstrated that TMEM doorway density after neoadjuvant therapy is a prognostic biomarker of breast cancer outcomes. In the initial development of the proposed TMEM MRI in humans, the tumor microenvironment is naïve to treatment. However, neoadjuvant therapy may affect the tumor microenvironment which could affect vascular anatomy - a key component of the TMEM MRI algorithm. Therefore, the study team aims to assess the correlation between TMEM doorway density and TMEM MRI activity after neoadjuvant therapy (Pilot Cohort C).

Вмешательства

• Устройство TMEM-MRI
  TMEM MRI INFORMATION: Unilateral breast MRI will be obtained on a 3.0T whole body MRI scanner with a dedicated breast radiofrequency coil. The patient will be scanned in the prone position with an in-dwelling IV catheter for a single dose contrast agent injection.
• Процедура FNA
  FNA: The patients who are recruited prior to biopsy (Cohort A) will have had TMEM-MRI performed prior to biopsy. They will then present to radiology for ultrasound-guided core biopsy of the breast mass. FNA will be performed during this procedure. The FNA will be performed after local anesthetic is administered but prior to insertion of the core biopsy needle. FNA will be performed by the radiologist under direct sonographic visualization of the mass. Five passes will be obtained with a 25-gauge

Первичные конечные точки

• Tumor permeability assessed by TMEM-MRI [Срок оценки: Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and signing of consent and 0-56 days before surgery]

Вторичные конечные точки (4)

• TMEM density in breast cancer patients [Срок оценки: Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes]
• MenaCalc [Срок оценки: Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes]
• MenaInv [Срок оценки: Cohort B: ~14 days following breast biopsy and consent. Cohort C: After neoadjuvant therapy and signing of consent analyses. Conducted on tissue sections from formalin-fixed paraffin-embedded breast cancer specimen resected for therapeutic purposes]
• Circulating Tumor Cells (CTCs) [Срок оценки: Cohort B: ~14 days following breast biopsy and signing of consent. Cohort C: After neoadjuvant therapy and consent and 0-56 days before surgery]

Критерии участия

Критерии включения

• For pre-pilot phase (MRI sequence development):

o Patients with a breast mass, with biopsy-proven histology of invasive breast carcinoma (any histologic type and ER,PR,HER2 status)

• For pilot phase Cohort A:

o Patients with a breast mass considered highly suspicious for invasive carcinoma by the radiologist (BIRADS 5).

• For pilot phase Cohort B:

• Patients with a breast mass found to be invasive ductal carcinoma on core biopsy.
• No preoperative therapy for the current breast cancer has been started (endocrine therapy, chemotherapy, or radiation). Patients can receive preoperative treatment after TMEM-MRI is conducted, if clinically indicated.
• For pilot phase Cohort C:

• Patients with locally advanced breast cancer, anatomic stage II-III, who received neoadjuvant therapy as per standard of care.
• Residual palpable mass > 1 cm in largest diameter after neoadjuvant therapy.
• Candidate for breast MRI before definitive surgery.
• Tumor size/breast mass should be > 1 cm in largest diameter (radiologically).
• Multifocal disease is allowed, as long as patients meet all eligibility criteria.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Willingness to undergo a "research breast MRI".
• Patient must be able to undergo MRI with gadolinium enhancement.

• No history of untreatable claustrophobia.
• No presence of non-MRI compatible metallic objects or metallic objects that, in the opinion of a radiologist, would make MRI a contraindication.
• No history of sickle cell disease.
• No contraindication to intravenous contrast administration.
• No known allergy-like reaction to gadolinium
• No known or suspected renal impairment. Glomerular Filtration Rate (GFR) should be greater than 30 mL/min/1.73 m2.
• Weight less than or equal to the MRI table limit.
• Ability to understand and willingness to sign a written informed consent.

Критерии исключения

• Patients may not have had breast cancer or radiation therapy to the ipsilateral breast in the past.
• No breast prosthetic implants (silicone or saline) are allowed.
• Use of any investigational agent within 30 days of starting study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study.
• Patients must be non-pregnant and non-lactating. Patients must have a negative pregnancy test (urine or serum) within 7 days of registration date.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 1 центр

• Montefiore Medical Center — The Bronx

Публикации

• Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90. doi: 10.3322/caac.20107. Epub 2011 Feb 4. PMID 21296855
• Hellman, S. and J.R. Harris, Natural history of breast cancer, in Diseases of the Breast., J.R. eds Harris, Lippman, M. E., Morrow, M. & Osborne, C. K., Editor. 2000, Lippincott Williams & Wilkins: Philadelphia. p. 407-23.
• Weigelt B, Peterse JL, van 't Veer LJ. Breast cancer metastasis: markers and models. Nat Rev Cancer. 2005 Aug;5(8):591-602. doi: 10.1038/nrc1670. PMID 16056258
• Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009 Nov 25;139(5):871-90. doi: 10.1016/j.cell.2009.11.007. PMID 19945376
• Fidler IJ, Poste G. The "seed and soil" hypothesis revisited. Lancet Oncol. 2008 Aug;9(8):808. doi: 10.1016/S1470-2045(08)70201-8. No abstract available. PMID 18672217
• Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009 Jun;119(6):1420-8. doi: 10.1172/JCI39104. PMID 19487818
• Warzecha CC, Carstens RP. Complex changes in alternative pre-mRNA splicing play a central role in the epithelial-to-mesenchymal transition (EMT). Semin Cancer Biol. 2012 Oct;22(5-6):417-27. doi: 10.1016/j.semcancer.2012.04.003. Epub 2012 Apr 23. PMID 22548723
• Ellis JD, Barrios-Rodiles M, Colak R, Irimia M, Kim T, Calarco JA, Wang X, Pan Q, O'Hanlon D, Kim PM, Wrana JL, Blencowe BJ. Tissue-specific alternative splicing remodels protein-protein interaction networks. Mol Cell. 2012 Jun 29;46(6):884-92. doi: 10.1016/j.molcel.2012.05.037. PMID 22749401

Идентификаторы

NCT: NCT03694756 · 2018-9529

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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